Randomized Clinical Trial of Prehospital Induction of Mild Hypothermia in Out-of-Hospital Cardiac Arrest Patients Using a Rapid Infusion of 4°C Normal Saline - Prehospital Hypothermia for OHCA


Hospital cooling (32-34°C) improves neurologic outcome after out-of-hospital cardiac arrest (OHCA), especially ventricular fibrillation (VF). It is unknown if institution of more rapid cooling (i.e., prehospital cooling) would have better outcomes compared to hospital alone cooling.

The current trial sought to determine whether prehospital cooling improves outcomes from cardiac arrest with VF or non-VF compared with hospital-only cooling.


Prehospital cooling would be superior to hospital cooling in patients with OHCA.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • ROSC
  • Tracheal intubation
  • Intravenous access
  • Successful placement of esophageal temperature probe
  • Unconsciousness

    Number of enrollees: 1,364
    Duration of follow-up: 30 days
    Mean patient age: 62 (VF), 68 (non-VF)
    Percentage female: 24% (VF), 45% (non-VF)


  • Traumatic cardiac arrest
  • Age believed to be <18 years
  • Being awake, following commands
  • Temperature of <34°C

Primary Endpoints:

  • Survival and neurological outcomes at discharge

Drug/Procedures Used:

Individual subjects were randomized to prehospital cooling with rapid infusion of 2 liters of 4°C normal saline after return of spontaneous circulation (ROSC), sedation and skeletal muscle relaxation, or standard care, which involved cooling on arriving to the hospital. Randomization was stratified by receipt of hospital cooling and first recorded rhythm (VF vs. non-VF).

Principal Findings:

A total of 1,364 patients were randomized. Of these, 583 had VF (292 to prehospital cooling and 291 to control) and 776 had non-VF (396 to prehospital cooling and 380 to control) rhythms. Baseline characteristics were different between patients with VF vs. non-VF, but fairly similar between the two randomized groups. Nearly three-quarters of patients with VF had a witnessed cardiac arrest, compared with 53% with non-VF rhythms. Similarly, cardiopulmonary resuscitation before emergency medical sysem arrival was performed in 66% of VF arrest patients and 52% of non-VF arrest patients. Sustained ROSC was noted in nearly 94% of VF patient and 90% non-VF patients.

The mean temperature at randomization was 36°C. There was a significant decrease in temperature at hospital arrival in the prehospital cooling arm (-1.2°C vs. -0.1°C for VF patients, -1.3°C vs. -0.1°C for non-VF patients, p < 0.001 for both). Patients randomized to prehospital cooling and who also received hospital cooling achieved a goal temperature by 4.2 hours, compared with 5.5 hours in patients who only received hospital cooling.

The primary endpoint of survival to hospital discharge was similar between the prehospital cooling and hospital-only cooling arms (62.7% vs. 64.3%, p = 0.69 for VF; 19.2% vs. 16.3%, p = 0.30 for non-VF). Of the patients discharged alive, discharge with mild or no neurological deficits was similar (57.5% vs. 61.8% for VF patients; 14.4% vs. 13.4% for non-VF patients). Other outcomes including pressors after randomization (9% vs. 9%) and in-field deaths (1.3% vs. 1.6%) were similar; re-arrest after randomization was slightly higher in the prehospital cooling arm (26% vs. 21%, p = 0.008). On arrival to the emergency department, there was a higher incidence of pulmonary edema on chest X-ray (41% vs. 30%, p < 0.001) and requirement for diuretics within 12 hours of hospital arrival (18% vs. 12%) in the prehospital cooling arm.


The results of this trial indicate that prehospital cooling with 2 liters of normal saline (with time to achieve goal temperature of 4.2 hours) is not superior to hospital-only cooling (time to achieve goal temperature of 5.5 hours) in patients with OHCA suffering both VF and non-VF arrests. Prehospital cooling resulted in greater pulmonary edema and re-arrest. Although survival to hospital discharge was high in both arms in patients with VF (nearly two-thirds), survival in patients with non-VF arrests remains abysmally low (<20%).

It is unknown if intra-arrest cooling, which would achieve therapeutic hypothermia sooner than 4 hours or prehospital cooling by other means such as a cooling blanket, thus potentially reducing pulmonary edema, might be associated with better outcomes. These strategies are currently under study.


Kim F, Nichol G, Maynard C, et al. Effect of Prehospital Induction of Mild Hypothermia on Survival and Neurological Status Among Adults With Cardiac Arrest: A Randomized Clinical Trial. JAMA 2013;Nov 17:[Epub ahead of print].

Presented by Dr. Francis Kim at the American Heart Association Scientific Sessions, Dallas, TX, November 17, 2013.

Keywords: Pulmonary Edema, Follow-Up Studies, X-Rays, Cardiopulmonary Resuscitation, Diuretics, Ventricular Fibrillation, Emergency Service, Hospital, Heart Arrest, Unconsciousness, Temperature, Intubation, Out-of-Hospital Cardiac Arrest, Hypothermia, Muscle Relaxation

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